Hand Over Hand

Quartz crystals from Herkimer County mines are made of exclusively right- or left-handed lattice structures.

Credit: J. Michael McBride

Sparkling Symbols

Quartz crystals from Herkimer County mines are made of exclusively right- or left-handed lattice structures.

Credit: J. Michael McBride

HERKIMER COUNTY is an unassuming sliver of land in upstate New York, but its rocky outcrops conceal a chemical phenomenon that’s common to all life on Earth.

It’s there that anyone with a chisel and a sense of adventure can trek to the local mines and dig up so-called Herkimer diamonds, which are actually quartz crystals with a diamond-like geometrical shape. At the molecular level, quartz is chiral—its crystals contain mirror-image chemical lattices that can be likened to a person’s left and right hands. “Most quartz crystals are mixtures of the right- and left-handed structures,” says J. Michael McBride, a physical organic chemist at Yale University who studies crystals. But there’s something special about the quartz at Herkimer—each crystal is exclusively left- or right-handed, something McBride’s team saw on a specimen-collecting journey to Herkimer several years ago.

Living things on Earth are like Herkimer diamonds. The molecules living things are made of, such as amino acids and nucleic acids, are overwhelmingly of one mirror image form, a phenomenon called homochirality. How single chirality emerged on Earth is a multilayered mystery that captivates scientists seeking to understand the origins of life.

In recent years, researchers have discovered chemical and physical ways to turn a tiny imbalance between the two chiral forms, or enantiomers, of a molecule into a near-total preference for one enantiomer. But possible solutions to that part of the problem beg the question of where the initial break in symmetry arose from in the first place. And potential explanations for that process are beginning to emerge as well.

One way of amplifying a small imbalance in chirality into homochirality is with a chemical reaction in which one enantiomer catalyzes its own formation while at the same time blocking formation of the other enantiomer. Chemical physicist Sir Frederick Charles Frank of Oxford University first proposed that idea (Biochim. Biophys. Acta1953,11, 459), but it took more than 40 years for an experimental version of his hypothetical reaction to surface. In 1995, a team led by chemist Kenso Soai of the Tokyo University of Science discovered that an organozinc catalyst can shepherd just such a reaction, which produces a near-homochiral alcohol (Nature1995,378, 767; C&EN, Nov. 30, 1998, page 9).

Although Soai’s discovery came more than 10 years ago, no one has found another reaction quite like it. “Such reactions are not easy to find because there are certain mechanistic conditions that have to be met,” says Svetlana Tsogoeva, a chemist from the University of Erlangen-Nuremberg, in Germany. Her team is examining two other reactions that are jockeying for membership in that exclusive club. It remains to be seen whether they’ll gain access.

In the absence of deliberate chiral influences such as chiral auxiliaries (chirality-inducing agents) or catalysts, Tsogoeva’s team saw some enrichment of one product enantiomer in an aldol reaction and in a Mannich reaction, which are both well-known carbon-carbon bond-forming processes (Angew. Chem. Int. Ed.2007, 46, 393; Chirality2007,19, 816; Angew. Chem. Int. Ed.2009, 48, 590).

Interstellar

Rosenberg peers into an experimental chamber in which he performs chiral-selective chemistry under outer-space-like, high-vacuum conditions.

Credit: Argonne National Laboratory

Interstellar

Rosenberg peers into an experimental chamber in which he performs chiral-selective chemistry under outer-space-like, high-vacuum conditions.

Credit: Argonne National Laboratory

THE OBSERVATIONS have generated a great deal of discussion in the community, says Günter von Kiedrowski, who studies complex chemical systems at Ruhr University, in Bochum, Germany. That’s because compared with the Soai reaction, aldol and Mannich reactions are more likely to work under conditions that prevailed on early Earth, he says. Soai’s reaction requires an organozinc catalyst and uses toluene as a solvent, which aren’t likely to have existed back then, he explains.

It isn’t clear that the mechanism behind Tsogoeva’s systems is similar to Soai’s. In collaboration with independent theoretician Michael Mauksch, Tsogoeva’s team is still trying to figure out a mechanism that explains their observations while simultaneously working on accelerating their process, which currently takes days. Regardless of the question of mechanism, Tsogoeva’s work should encourage researchers to search for additional chemical reactions that can amplify one enantiomer to dominance, von Kiedrowski says.

Besides exploring how chemical reactions could reach homochirality on their own, researchers have analyzed how to achieve it by coupling chemical reactions to the physical process of crystallization.

Last year, for instance, chemist Donna G. Blackmond of Imperial College London and her collaborators reported a way to convert a nearly racemic amino acid derivative into chirally pure crystals. She teamed with DSM Pharmaceutical Products, the contract research company Syncom, and Elias Vlieg of Radboud University Nijmegen, all in the Netherlands.

The group started with a mixture of crystals that had a small enantiomer imbalance. They subjected a slurry of those crystals to stirring and abrasive grinding, which continually wears away the crystals, and included a catalytic amount of base, which helps the chiral compound switch between its mirror image forms in solution, a process called racemization. Whichever enantiomer was in excess in the starting crystal composition ended up as the winner—it was the molecule making up the chirally pure crystals that emerged (J. Am. Chem. Soc. 2008,130,1158; Cryst. Growth Des.2008, 8, 1675; C&EN, Aug. 4, 2008, page 12). “Were Frank alive today, he would be delighted by these observations because the crystallization fits his model for amplification of a single-handed entity,” Yale’s McBride wrote in a commentary on the work (Nature2008,452, 161).

The Europe-based team’s study was inspired by an earlier observation by Cristobal Viedma of Complutense University, in Madrid, who obtained chirally pure crystals of an inorganic compound, sodium chlorate (Phys. Rev. Lett.2005,94, 065504). That salt is not chiral in solution but can form chiral crystals, much as quartz can. Extending Viedma’s work to chiral molecules became a reality when the team realized that fast racemization in solution might make a chiral molecule adopt similar crystallization behavior, Blackmond explains.

MORE RECENTLY, Viedma teamed with Blackmond to obtain chirally pure crystals of aspartic acid, an amino acid, through a process similar to the one Blackmond used with her Dutch collaborators (J. Am. Chem. Soc.2008,130, 15274). Blackmond says it’s exciting to see the technique work on an actual amino acid that could presumably have been around on early Earth, as opposed to a model compound. The team is now working on developing quantitative models that describe some of their new observations.

Whether based on physical or chemical changes, amplification methods rely on there being a tiny excess of one enantiomer at the start of the process. However, these methods don’t address where that imbalance might have come from on early Earth. Last year, researchers led by Ronald Breslow of Columbia University described chemistry that might explain how meteorites could have brought an enantiomer imbalance to Earth from the depths of space.

Breslow was inspired by the small excess of left-handed α-methyl amino acids that astrobiologist Sandra Pizzarello of Arizona State University found in the Murchison meteorite, which crashed to Earth in 1969. He suspected that α-methyl amino acids, which cannot interconvert between their two mirror-image forms, might have been the seeds of chirality that allowed left-handed amino acids to thrive and become the dominant enantiomer they are today.

Chirally pure crystals of aspartic acid materialize from a system in which the crystals are in equilibrium with a solution phase that can switch between enantiomers.

Emerging Handedness

Chirally pure crystals of aspartic acid materialize from a system in which the crystals are in equilibrium with a solution phase that can switch between enantiomers.

To demonstrate how that may have happened, Breslow’s team adapted an amino group transfer reaction previously reported by their group. The reaction transfers chiral information from the starting materials, α-methyl amino acids, to the products, which are normal amino acids with the same handedness as that in all living things. Although the reaction gives only a modest excess of one enantiomer, the team successfully converted that small excess to near homochirality (Org. Lett.2008,10, 2433). In subsequent studies the team has achieved similar amplification effects with nucleosides, the building blocks of RNA, Breslow tells C&EN.

Even if meteors brought an initial imbalance of chirality to Earth, that still doesn’t explain how the meteors had an imbalance in the first place. Breslow’s 2008 study invokes a theory first put forward by a team led by the late William A. Bonner, a Stanford University chemist. Bonner and his coworkers proposed that amino acids could have encountered circularly polarized ultraviolet light, a type of radiation that produces a slight enantiomeric excess (Nature1983,306, 118).

WORK FROM a team at Argonne National Laboratory suggests that electrons generated in space are another feasible source of that first chiral imbalance (Phys. Rev. Lett.2008,101, 178301). There, Richard A. Rosenberg and coworkers exposed a magnetic material placed under high vacuum to ionizing radiation from an X-ray light source, which generates low-energy electrons with spins aligned in one direction. They demonstrated that these low-energy electrons can break the carbon-oxygen bond in 2-butanol, a simple chiral molecule that they adsorbed on their magnetic material, a nickel-iron alloy. The bond-cleaving rate is significantly faster for one enantiomer than the other. Which enantiomer ends up winning depends on the direction of the low-energy electrons’ spin, which is determined by the magnetic material’s magnetic dipole moment.

Perhaps the biggest challenge for origin-of-homochirality studies in the future will be to move away from thinking about the field in isolation, Imperial College’s Blackmond says. Chirality alone doesn’t tell the story of how life began—there are also unanswered questions about molecular complexity and self-replicating systems, for example. “It’s neat to show that you can make pure left-handed or right-handed crystals,” she says. “It’s a harder problem to think about where we go from there.”